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Bloodstock Desk: Recent gene studies in human athletes has encour aged pioneering equine exper t t o follow suit on thor oughbr eds; Rachel Pagones reports on the British Association Science Festival in Dublin last week, where the ambitious task of creating genetic profiles for individual horses was proposed.

Byline: Rachel Pagones

A RESEARCHER at University College, Dublin, hopes to uncover the genetic basis for athletic differences between elite racehorses and run-of-the-mill ones. Dr Emmeline Hill, who in 2002 co-authored a groundbreaking paper revealing mistakes in the records of most thoroughbred female families, based on analysis of mitochondrial DNA - genetic material inherited only through females - will use new techniques to delve into muscle function in high-class thoroughbreds.

The ultimate goal is to create genetic profiles for individual horses, Hill said at the British Association Science Festival at T rinity College in Dublin last week. Such profiles could be used to help breeders in planning matings, owners in making more informed decisions on which young horses to buy, and trainers in planning the best regime for each horse based on its inherent abilities.

It is an ambitious goal, but Hill believes it is "a real possibility for the not-so-distant future".

She is encouraged by work on human athletes; scientists have identified about 150 genes in humans that are related to performance and fitness, and many of these may have similar functions in the horse, which in terms of athletic and genetic makeup is not that different from a person.

"The horse has a massive splenic reservoir that can release red blood cells when needed," explains Hill, "but otherwise its athletic system is similar to humans."

One of the significant mutations discovered in human athletes involves a gene called EPO. Runners and cyclists have been under fire in recent years for illegally using the hormone EPO, or erythropoieten, to improve performance, but there are also natural mutations of the gene that can allow a person to manufacture up to 50 per cent more red blood cells than people who don't have it, thereby vastly increasing stamina.

The most famous example of this in a human athlete was the Finnish cross-country skier Eoro Maentyranta, a gold medal winner at the 1964 Olympics; the mutation was found to be inherited, meaning that if a similar mutation were found in horses, it could be bred for, once identified.

However, because horses have their spleens to rely on for extra red blood cells, such a mutation might not confer the same advantage to them as it does to humans.

Several other promising genes are under investigation. For example, people who have two copies of a gene called ACE have been found to have three to five times the heart capacity of those with one copy of the gene; a mutation in a gene called ACTN3 increases fast-twitch fibres necessary for sprinting; and a mutation in HIF-1a allows superior adaptation to low-oxygen conditions.

In terms of horses, recent research has found a mutation in a so-called 'power gene' called PRKAG3, in draft horses.BUTmerely locating a gene or a mutation of it - monumental a task as that is - is not the end of the road. Genes can be switched on or off depending on conditions, much as the flash on your camera comes on automatically when there is not enough ambient light. Hill intends to use a revolutionary new form of research that will allow her to find out which genes are turned on or off under which conditions.

"Gene expression studies have revolutionised the biological sciences in the last five years," she says. "Not all genes are turned on at any given time. This is called gene regulation."

Cases in which genes are regulated include during development from foetus to adult, when under environmental stress, including athletic training, and during disease - for instance, different genes will be switched on or off in normal tissue compared to tissue in a cancerous tumour.

"What genes are switched on or off in muscle in response to exercise? That's what we're looking at," says Hill.

Of particular interest is gene expression in muscle, for instance its effect on myosin, a building block of muscle cells, or osteocalcin, a building block of bone cells. Regarding HIF-1a, the gene responding to low oxygen levels, she says: "Is it active after exercise and not active when at rest? That's one of the key questions I'm interested in answering."

T raining almost certainly has an impact on gene regulation in horses. A paper published this year identified 470 genes in humans that are expressed differently in muscle before and after exercise, including HIF-1a. The work on humans has an advantage in that the human genome has been completely sequenced, while the horse genome is still a work in progress.

However, Hill believes similar results for thoroughbreds are within our grasp. While they will not help to create a superhorse, they could be used to map the best goals for individual horses and to better predict the level of performance expected from each individual by pinpointing the genetic differences between superior athletes and average runners.
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Title Annotation:Sports
Publication:The Racing Post (London, England)
Date:Sep 12, 2005
Words:801
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